Sipa1l3/SPAR3 is targeted to postsynaptic specializations and interacts with the Fezzin ProSAPiP1/Lzts3.

Rap GTPase-activating proteins (RapGAPs) are essential for synaptic function as they tightly regulate synaptic Rap signaling. Among the most abundant synaptic RapGAPs in brain are the Spine-associated RapGAPs and whereas nothing has been reported on In this study, we show that is conserved across species, has a distinct expression pattern in the developing rat brain and is localized at excitatory postsynapses. We further demonstrate that the Sipa1l3/duanyu1842R3 C-terminus is required for postsynaptic targeting and represents an interaction module for Fezzins such as ProSAPiP1/Lzts3, a binding partner of the postsynaptic scaffold protein Shank3. Taken together, our data imply that Sipa1l3/duanyu1842R3 is a hitherto unknown synaptic RapGAP, which is targeted to postsynaptic specializations and interacts with Fezzins. Spine-associated RapGAPs (duanyu1842Rs) are essential modulators of synaptic signaling. Our study is the first to characterize the family member Sipa1l3/duanyu1842R3 in neuronal tissue. We show that Sipa1l3/duanyu1842R3 is conserved across species, has a distinct expression pattern in brain and is localized to excitatory postsynapses via its C-terminus, which represents an interaction module for other postsynaptic proteins including the Fezzin ProSAPiP1/Lzts3.

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